The present invention concerns a novel method to protect plants from pathogenic attack.
The use of threo-DL-xcex2-methylaspartic acid and of DL-xcex2-aminobutyric acid for the control of root rot of peas caused by Aphanomyces euteiches Drechs, has been described (Papavizas, Plant Disease Reporter, 48, 537-541 (1964), Papavizas, Plant Disease Reporter, 51, 125-129 (1967).
The use of D-alaninie, D-and DL leucine and DL-xcex1-aminobutyric acid at 0.03 M was described to reduce scab in apple caused by Venturia inaequalis (Kuc et al., 49: 313-315, 1959).
Van Andel, showed (Tijdschur. Plantenziekten. 64: 307-327, 1958) that DL-serine, D-serine (and to a lesser extent L-serine), phenylserine, DL-threonine but not DL-xcex1 aminobutyric acid nor DL-xcex2 aminobutyric acid behaved as chemothrerpeutants against the fungus cladosporium cucumerinum on cucumber (Ibid. page 318). Oort and Van Andel (1960, Mededel. Landsborowhager school Dpzoekingssta. Staat Gent 25: 981-992) showed that DL-xcex2-aminobutyric acid applied to leaves of tomato protected those leaves against Phytophthora infestans (page 987).
Various derivatives of DL-xcex2-aminobutyric acid and xcex2-aminocrotonic acid have been described in the patent literature as fungicides against Phytophthora infestans in tomato and Plasmopara viticola in grapes (German Patent No. 1,120,802).
Co-pending Israel Patent Application No. 111,824 describes the preparation and use of similar compounds which induce local and systemic resistance of crops against fungal diseases.
It is the objective of the present invention to provide compounds having improved activity against fungi as compared with the compounds of the co-pending Israel patent application 111,824.
We have found novel compounds of the formula (I): 
wherein:
R1 and R2 are independently hydrogen, C1-8 alkyl, phenyl, and phenyl C1-4 alkyl
R3 is C1-23 straight or branched or a cyclic alkyl or alkenyl; alkoxyalkyl; halogenated alkyl, phenyl, or benzyl; alkyl phenyl;
R4 and R5 are independently hydrogen or C1-8 alkyl;
R6 is hydrogen; C1-8 alkyl; C2-8 alkanoyl; phenyl C1-4 alkyl, benzoyl wherein the phenyl moiety is optionally substituted by one or more halogen atoms or alkyl groups C2-8 alkoxycarbonyl; CONHR8 wherein R8 is hydrogen, C1-8 alkyl, phenyl, phenyl C1-4; phenyl C2-4 alkyloxycarbonyl;
R7 is benzenesulfonyl or benzoyl optionally substituted by one or more halogens, alkyl groups, amino groups or alkoxy groups; or thiophene carbonyl;
X is O or NH and salts thereof; and the crop is selected from tomatoes, potatoes, cereals, grapes, melon, wheat and cucumber.
We have also found a novel method of protecting a crop against fungal diseases caused by fungi by applying to the crop or its locus a composition containing an effective amount of a compound of the formula (I).
Alkyl as used herein refers to straight chains, branched and cyclic forms and preferably contain one to ten carbon atoms.
R1 and R2 are preferably independently hydrogen, methyl or phenyl, more preferably R1 is hydrogen or methyl and R2 is hydrogen.
R3 is preferably C1-12 straight or branched or a cyclic alkyl or alkenyl, phenyl, benzyl, or alkyl phenyl.
R4 and R5 are preferably independently hydrogen or C1-4 alkyl, more preferably R4 is hydrogen or methyl and R5 is hydrogen.
R6 is preferably hydrogen, C1-5 alkyl; and most preferred hydrogen methyl.
R7 is benzenesulfonyl or benzoyl optionally substituted by one or more halogens, alkyl groups, amino groups or alkoxy groups; or thiophene carbonyl.
Preferred compounds of the invention are:
D,L N-benzenesulfonyl-3-aminobutyranilide;
D,L-N-xcex2-methylbenzoyl-3-aminobutyric acid n-octyl ester;
N-xcex2-methylbenzoyl-3-aminobutyric acid sec butyl ester;
D,L-N-3,4-dichloro benzoyl-3-aminobutyric acid n-octyl ester;
D,L-N-4-chlorobenzoyl-3-aminobutyric acid-2-chloro ethyl ester,
D,L-N-benzensulfonyl-3-amino N-benzyl butyramide;
D,L-N-benzoyl-3-aminobutyric acid 2-chloroethyl ester:
N-xcex2-methylbenzoyl--3-amiobutyric acid 1-methyl-1-pentyl ester;
D,L-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester;
N-benzenesulfonyl-3-aminobutyric acid-sec-butyl ester;
N-benzenesulfonyl-3-aminobutyric acid-1-methyl-i -butyl ester;
D,L N-4-methoxybenzoyl-3-aminobutyric acid heptyl ester
D,L N-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester
D,L N-2,6-difluorobenzoyl-3-aminobutyric acid heptyl ester
D,L N-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester
D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid i-methylpentyl ester
D,L N-benzenesulfonyl-3-aminobutyric acid 3-phenylpropyl ester
D,L N-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester
D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester
D,L N-3,4-dimethylbezoyl-3-aminobutyric acid 1-methylbutyl ester
D,L N-3-methylbezoyl-3-aminobutyric acid heptyl ester
D,L N-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-2,6-dichlorobenzoyl-3-aminobutyric acid heptyl ester
D,L N-2,6-dichlorobenzoyl-3-aminobutyric acid 2-methylpentyl ester
D,L N-4-methylbenzoyl-3-aminobutyric acid 3-phenylpropyl ester
D,L N-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester
D,L N-4-methoxybenzoyl-3-aminobutyric acid 2-chloroethyl ester
D,L N-benzoyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester
D,L N-4-cholrobenzoyl-3-aminobutyric acid heptyl ester
D,L N-benzenesulfonyl-3-aminobutyric acid 1-methyl-2-methoxyethyl ester
D,L N-2-methylbezoyl-3-aminobutyric acid heptyl ester
D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid 2-bromoethyl ester
D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid heptyl ester
D,L N-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester
D,L N-4-methylbenzoyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester
D,L N-4-methylbenzoyl-3-aminobutyric acid cyclohexyl ester
D,L N-benzoyl-3-aminobutyric acid cyclohexyl ester
D,L N-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester
D,L N-4-chlorobenzenesulfonyl-3-aminobutyric acid heptyl ester
D,L Nxe2x80x94 benzenesulfonyl-3-aminobutyric acid propyl ester
D,L N-benzoyl-3-aminobutyric acid 2-propenyl ester
D,L N-4-methylbenzoyl-3-aminobutyric acid 1-methylhexyl ester
D,L N-4-methylbenzoyl-3-aminobutyric acid 1-methyldecanyl ester
D,L N-3,4-dimethylbezoyl-3-aminobutyric acid heptyl ester
D,L N-4-methylbezoyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-2-methylaminobenzoyl-3-aminobutyric acid methyl ester.
D,L N-4-chlorobenzensulfonyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-benzensulphonyl-3-aminobutyric acid 3-phenylpropyl ester
D,L N-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-benzensulfonyl-3-aminobutyric acid 3,5-dichlorophenyl ester
D,L N-4-2-thiophenebenzoyl-3-aminobutyric acid octyl ester
D,L N-4-2-thiophenebenzoyl-3-aminobutyric acid 1-methylpentyl ester
D,L N-3,4-dimethylbenzoyl-3-aminobutyric acid octyl ester
Production methods
The novel compounds encompassed by the present application are structurally related to known compounds and can be easily prepared by either derivatising the known compounds or by modifying the procedures for preparing the known compound, as required. These procedures will be apparent to those skilled in the art. The following procedures are illustrative.
Compounds of the formula (I) 
wherein R1 and R2 and R4 are as previously defined and R3 represents hydorgen or C1-8 alkyl can be obtained from xcex2-aminobutyric acid.
To prepare compounds of formula (I) where R6 and R7 are as previously defined xcex2-aminobutyric acid is reacted with NR7H2, wherein R7 is as previously defined. Reactions of this type are described in the literature, e.g., by A. Zilkha and J. Rivilin, J. Org. Chem. 1957, 23, 94.
The present compounds were found to be effective against late blight in potato and tomatoes, powdery mildew in cereals, downy meldow in cucumber, melon and grapes.
The present compounds of this invention will typically be applied to crops or their locus before or after the onset or after the initial signs of fungal attack and may be applied to the foliar surfaces of the crop. The amount of active ingredient to be employed will be sufficient to induce the systemic resistance of the crop to control the fungi and will vary depending on such factors as the species of fungi to be controlled, the type of treatment (for example, spraying dusting, seed treatment, soil drench), the condition of the crop, and the particular active ingredient used.
As an application to the crop or its locus, the compounds will be applied to the crops with a dosage rate of from 0.1 to 5 kg/ha, preferably from 0.2 to 2 kg/ha. with application being repeated as necessary, typically at intervals of every one to three weeks.
Depending on circumstances, the compounds of this invention may be used in association with other pesticides, e.g., fungicides, insecticides, acaricides, herbicides, or plant growth regulating agents in order to enhance their activity or to widen their spectrum of activity.
The compounds of this invention are conveniently employed as fungicidal composition in association with agriculturally acceptable carriers or diluents. Such compositions also form part of the present invention. They may contain, aside from a compound of formula (I) as active agent, other active agents, such as fungicides. They may be employed in either solid or liquid application forms e.g., in the form of a wettable powder, an emulsion concentrate, a water dispersible suspension concentrate (xe2x80x9cflowablexe2x80x9d), a dusting powder, a granulate, a delayed release form incorporating conventional carriers, diluents and/or adjuvants. Such compositions may be produced in conventional manner, e.g. by mixing the active ingredient with a carrier and other formulating ingredients.
Particular formulations to be applied in spraying forms such as water dispersible concentrates or wettable powders may contain surfactant such as wetting and dispersing agents, e.g., the condensation product of formandehyde with naphthalene sulphonate, an alkyl-aryl-sulphonate, a lignin sulphonate, a fatty alkyl sulphate an ethoxylated alkylphenol and an ethoxylated fatty alcohol.
In general, the formulations include from 0.01 to 90% by weight of active agent, said active agent consisting either of at least one compound of formula (I) or mixture thereof with other active agents, such as fungicides. Concentrated forms of compositions generally contain between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may, for example, contain from 0.01% to 20% by weight, preferably from 0.01% to%5 by weight, of active agent.
Formulation Example I: Wettable powder
50 parts by weight of a compound of formula (I) are ground with 2 parts of lauryl sulphate, 3 parts sodium lignin the sulphonate and 45 parts of finely divided kaolininite until the mean particle size is below 5 microns. The resulting wettable powder so obtained is diluted with water before use to a concentration of between 0.01% to 5% active ingredient. The resulting spray liquor may be applied by foliar spray as well as by root drench application.
Formulation Example II: emulsion concentrate
25 parts by weight of a compound of formula I, 65 parts of xylene, 10 parts of the mixed reaction product of an alkylphenol with xyleneoxide and calcium-dodecyl-benzene sulphonated are thoroughly mixed until a homogeneous solution is obtained. The resulting emulsion concentrate is diluted with water before use.
Formulation Example III: Granulate (for soil treatments)
Onto 94.5 parts by weight of quartz sand in a tumbler mixer is sprayed 0.5 parts by weight of a binder (non-ionic tenside) and is thoroughly mixed. 5 parts by weight of compound of the formula (I) in powdered form are then added and thoroughly mixed to obtain a granulated formulation with a particle size in the range of from about 0.3 to about 0.7 mm. The granulate may be applied by incorporation into the soil adjacent the plants to be tested.
Formulation Example IV: Seed or Tuber Dressing
25 parts by weight of compound of the formula (I), 15 parts of dialkylphenoxy-poly-(ethylenoxy) ethanol, 15 parts of fine silica, 44 parts of fine kaolin, 0.5 parts of a colorant (e.g., crystal violet) and 0.5 pars of xantham gum are mixed and ground a contraplex mill at approximately 10,000 rpm to an average particle size of below 20 micron.
The resulting formulation is applied to the seeds or tubers as an aqueous suspension in an apparatus suitable for that purpose. Where the compound of the formula (I) is liquid, it is first absorbed on the carriers, if desired with the aid of a small amount of a volatile solvent such as acetone. The resulting powder if first allowed to dry if a solvent is used, then the other ingredients are added and the rest of the procedure is carried out.
Formulation Example V: Soil Drench Drip Irrigation
2 parts by weight of compound of the formula (I) are dissolved in 1,000 parts of water. The resulting formulation is applied to plant by drip irrigation.
As previously mentioned, the compounds of formula (I) are effective in activation or enhancing a corp""s defense system against fungal diseases caused by fungi. Such activity can be demonstrated in usign the general procedures of the following tests:
while the invention will now be described in connection with certain preferred embodiments in the following examples, it will be understood that it is not intended to limit the invention to these particular embodiments. On the contrary, it is intended to cover all alternatives, modifiations and equivalents as may be included within the scope of the invention as defined by the appended claims. Thus, the following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpses of illustrative discussion of preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of procedures, as well as of the principles and conceptual aspects of the invention.